Selective ortho‐Functionalization of Adamantylarenes Enabled by Dispersion and an Air‐Stable Palladium(I) Dimer

• Published in: Angewandte Chemie International Edition Vol. 59; no. 20; pp. 7721 - 7725
• Main Authors: Kalvet, Indrek, Deckers, Kristina, Funes‐Ardoiz, Ignacio, Magnin, Guillaume, Sperger, Theresa, Kremer, Marius, Schoenebeck, Franziska
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 11-05-2020; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Alkylation; chemoselectivity; Communication; Communications; Cross coupling; DFT calculations; Dimers; Dispersion; homogeneous catalysis; Palladium; Steric hindrance; cross-coupling; chemoselectivity; palladium; homogeneous catalysis; DFT calculations
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202001326

Contrary to the general belief that Pd‐catalyzed cross‐coupling at sites of severe steric hindrance are disfavored, we herein show that the oxidative addition to C−Br ortho to an adamantyl group is as favored as the corresponding adamantyl‐free system due to attractive dispersion forces. This enabled the development of a fully selective arylation and alkylation of C−Br ortho to an adamantyl group, even if challenged with competing non‐hindered C−OTf or C−Cl sites. The method makes use of an air‐stable PdI dimer and enables straightforward access to diversely substituted therapeutically important adamantylarenes in 5–30 min.
It takes two: Contrary to the general belief that Pd‐catalyzed cross‐couplings at sites of severe steric hindrance are disfavored, it is shown that the oxidative addition to C−Br ortho to an adamantyl group is as favored as the corresponding adamantyl‐free system due to attractive dispersion forces. This enabled the development of a fully selective arylation and alkylation of C−Br ortho to an adamantyl group using an air‐stable PdI dimer.